Is TBCD p.Pro604Ser (c.1810C>T) pathogenic?

TBCD p.Pro604Ser (c.1810C>T) is classified Benign in TBCD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-11). AlphaMissense: likely benign (0.1553); Rare (popmax 0.549%, eas).

How common is TBCD p.Pro604Ser (c.1810C>T) in the general population?

TBCD p.Pro604Ser (c.1810C>T) is rare (popmax 0.549%, eas) (gnomAD).

What do computational predictors say about TBCD p.Pro604Ser (c.1810C>T)?

AlphaMissense predicts likely benign (score 0.1553) — an in-silico prediction, not a clinical call.

TBCD p.Pro604Ser

c.1810C>T · rs575721383 · VCV2060044

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1553 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.549%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1553	likely benign
REVEL	0.329	indeterminate
SaProt	LLR -11.04	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 190 kb · p 9.5e-05 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.549% East Asian · 246/44,788 alleles

Filtering AF 0.493% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.471%

Overall 0.0161% 259/1,610,928 alleles · rare exomes 215/1,458,558 · genomes 44/152,370 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.549%	182
Remaining individualsnot grpmax-eligible	0.0112%	8,910
South Asian	0.00443%	22,558
Admixed American	0.00168%	59,686
European (non-Finnish)	8.49e-05%	1,178,443

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TBCD
Protein: p.Pro604Ser
Coding: c.1810C>T
MANE Select: NM_005993
dbSNP: rs575721383
Type: single nucleotide variant
Location: chr17:82905941 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.45 · 6 PDB

Full TBCD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TBCD p.Pro604= Likely benign ★ same residue
TBCD c.1224-2A>G Pathogenic/Likely pathogenic ★★ same type
TBCD c.2007-2A>G Likely pathogenic ★★ same type
TBCD p.Ala475Thr Pathogenic/Likely pathogenic ★★ same type
TBCD p.Ala554Val Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg113Ter Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg303Ter Pathogenic/Likely pathogenic ★★ same type
TBCD p.Arg323Ter Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/tbcd-p-pro604ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown